Pregnancy malaria is thought to kill hundreds of thousands of African infants each year, but the impact of pregnancy malaria on infant health and malaria susceptibility has been poorly studied. Our longitudinal cohort studies in mother-infant pairs indicate that placental malaria increases the frequency of parasitemia during infancy, delays infant development, and increases the frequency of hospitalization during early life, and that proinflammatory molecule levels in cord blood are independently associated with delayed anthropometric development during infancy. This proposed Project will examine the impact of pregnancy malaria on malaria susceptibility and clinical outcomes during infancy and early childhood, in the context of a randomized trial of four Intermittent Preventive Treatment (IPTp) regimens against pregnancy malaria. This research is based on the following hypotheses: sulfadoxinepyrimethamine (SP) alone will be less effective than other IPTp regimens for preventing placental infection and inflammation; infants born to mothers receiving SP will be parasitemic at an earlier age and with greater frequency than other infants; infants born to mothers receiving SP will experience increased rates of hospitalization and malaria-related hospitalization compared to other infants; compared to other infants, infants born to mothers receiving SP will suffer delayed growth during infancy. Randomized IPTp trials offer a unique opportunity to study the impact of pregnancy malaria on infant outcomes, by clearly stratifying women into groups with different levels of exposure defined in the course of the trial. Based on our hypotheses and Preliminary Results, we expect the following outcomes: placental malaria and fetal inflammatory responses will be more common in the SP group, and placental malaria will increase risk of parasitemia and hospitalization during infancy, while both placental malaria and cord inflammation will be related to delayed anthropometric development of the infant. These studies will establish the mechanisms underlying increased infant mortality related to pregnancy malaria, and may illuminate long-term effects of in utero inflammation on health and development during early childhood.